Dialkylamino esters of benzopyranopyridines

ABSTRACT

WHEREIN R1 IS HYDROGEN LOWERALKANOYL, CYCLOALKYLLOWERALKYL, LOWERALKYL, CYCLOALKYLLOWERALKANOYL, LOWERALKENYL, LOWERALKYNYL, HALOLOWERALKENYL, PHENYLLOWERALKYL, PHENYLLOWERALKENYL OR PHENYLLOWERALKNYL; R2 IS LOWERALKYL; R3 IS C1-C20 ALKYL OR CYCLOALKYLLOWERALKYL; N IS AN INTEGER FROM 1 TO 6; AND R4 IS HYDROGEN OR LOWERALKYL; AND THE PHARMACEUTICALLY ACCEPTALE ACID ADDITION SALTS THEREOF. TETRAHYDRO-5H-(1)BENZOPYRANO(4,3-C)PYRIDINE   2-R1,5,5-DI(R-),8-R3,10-((R4-)2-N-(CH2)N-COO-)-1,2,3,4-   DIALKYLAMINO ESTERS OF BENZOPYRANOPYRIDINES REPRESENTED BY THE FORMULA

United States Patent 3,787,424 DIALKYLAMINO ESTERS 0F BENZOPYRANO- PYRIDINES Harry George Pars, Lexington, and Raj Kumar Razdan,

Belmont, Mass., assignors to Sharps Associates, Cambridge, Mass. No Drawing. Filed May 8, 1972, Ser. No. 251,618 Int. Cl. C07d 31/34 US. Cl. 260-295 T 6 Claims ABSTRACT OF THE DISCLOSURE Dialkylamino esters of benzopyranopyridines represented by the formula wherein R is hydrogen, loweralkanoyl, cycloalkylloweralkyl, loweralkyl, cycloalkylloweralkanoyl, loweralkenyl, loweralkynyl, haloloweralkenyl, phenylloweralkyl, phenylloweralkenyl or phenylloweralkynyl; R is loweralkyl; R is C -C alkyl or cycloalkylloweralkyl; n is an integer from 1 to 6; and R is hydrogen or loweralkyl; and the pharmaceutically acceptable acid addition salts thereof.

DETAILED DESCRIPTION OF THE INVENTION This invention relates to dialkylamino esters of 'benzopyranopyridines, to compositions containing the compounds and to methods for preparing and using the compounds.

The compounds of this invention are represented by the formula wherein R is hydrogen, loweralkanoyl, cycloalkylloweralkyl, loweralkyl, cycloalkylloweralkanoyl, loweralkenyl, loweralkynyl, haloloweralkenyl, phenylloweralkyl, phenylloweralkenyl or phenylloweralkynyl; R is loweralkyl; R is 0 -0 alkyl or cycloalkylloweralkyl; n is an integer from 1 to 6; and R is hydrogen or loweralkyl; and the pharmaceutically acceptable acid addition salts thereof.

The term loweralkyl, as used herein, refers to C -C straight or branched chain alkyl groups including methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, n-hexyl and the like.

The term loweralkenyl refers to straight and branched chain C C alkyl radicals from which a hydrogen atom has been removed from each of two adjacent carbon atoms to produce ethylenic unsaturation; e.g., vinyl, allyl, methallyl, l-pentenyl and the like.

The term loweralkynyl refers to C -C alkyl groups as defined above, from which two hydrogen atoms have been removed from each of two adjacent carbon atoms to produce acetylenic unsaturation; e.g., ethynyl, propargyl, Z-butynyl, l-pentynyl and the like.

The term halo includes chloro, fluoro, bromo and iodo.

3,787,424 Patented Jan. 22, 1974 The term loweralkanoyl refers to saturated, monovalent, aliphatic radicals derived from a monocarboxylic acid, including straight or branched chain radicals of from one to six carbon atoms including formyl, acetyl, propionyl, m-methylpropionyl, butyryl, hexanoyl and the like.

Cycloalkyl, as used herein, refers to cyclic, saturated aliphatic radicals of from three to eight carbon atoms, such as cyclopropyl, cyclobutyl, cyclohexyl and cyclooctyl.

Cycloalkylloweralkyl refers to groups such as cyclopropylmethyl, Z-methylcyclobutyl and the like.

The term C -C alkyl refers to straight and branched chain alkyl radicals having from one to twenty carbon atoms such as methyl, n-amyl, 3-methy1-2-octyl, 2- nonyl, 2-eicosanyl and the like.

The term acid addition salts refers to non-toxic salts prepared by reacting a basic ester of a benzopyranopyridine with an organic or inorganic acid, or by reacting a benzopyranopyridine with a salt of an appropriate acid. Representative salts include the hydrochloride, hydrobromide, sulfate, bisulfate, acetate, valerate, oleate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, succinate, tartrate, napsylate and the like. Such salts are well known in the art and are considered to be pharmaceutically acceptable.

As used herein, the terms phenylloweralkyl, phenylloweralkenyl, and phenylloweralkynyl mean a monovalent radical consisting of a phenyl nucleus bonded to the rest of the molecule, respectively, through a divalent loweralkylene radical of from one to four carbon atoms as illustrated by, but not limited to methylene, 1,1-ethylene, 1,2-ethylene, 1,3-propylene, 1,2-pyropylene, 1,4-butylene and the like or through a divalent loweralkenylene radical of from two to four carbon atoms, as illustrated by, but not limited to 1,2-ethenylene, 1,3-(l-propenylene), 1,3- (l-butenylene), 1,4-(2-butenylene) and the like, or through a divalent loweralkynylene radical of from two to four carbon atoms, as illustrated by, but not limited to 1,2-ethynylene, 1,3-propynylene, 1,3-(1-butynylene) and the like. Here and elsewhere throughout this specification, it will be understood the benzene ring of phenyl can bear any number and kind of substituents such as would occur to the man skilled in organic chemistry. Solely for illustration, and without limitation, such substituents include loweralkyl, loweralkoxy, halo(chloro, bromo, iodo, or fluoro), nitro, loweralkylmercapto and the like.

The compounds of this invention are useful as antidepressant agents at dosages of 0.5 to 250 mg/kg. of body weight daily. The anti-depressant activity was first established using the modified dopa test (Fed. Proc. 23, p. 198 (1964). The compounds also exhibit tranquilizing overtones which makes them particularly useful in treating depression where agitation is One of the manifested symptoms.

Presently preferred compounds are those Where R is alkynyl.

Generally speaking, the esters of this invention are prepared by reacting equimolar quantities of the corresponding benzopyranopyridines, a carbodiimide such as dicyclohexylcarbodimide, and the appropriate acid or its salt in a suitable solvent such as methylene chloride, chloroform and the like.

The reaction mixture is filtered to remove the byproduct of dicyclohexylurea, and the solvent can be distilled off using a rotary evaporator. The residue can be directly crystallized from suitable solvents such as benzene/ether or the residue can be chromatographed and the desired material isolated from the appropriate chromatographic fractions. If the acid rather than the acid salt is reacted with the benzopyranopyridine, the desired acid addition salt of the basic ester can be prepared by methods well known in the art.

The preferred reaction is represented by the following reaction sequence:

wherein R R R and R are as defined above and R is The preparation of the benzopyranopyridines of Formula I is disclosed in US. Pat. No. 3,576,798 and 3,429,- 889.

The following examples further illustrate the present invention:

EXAMPLE 1 5,5-dimethyl [4(diethylamino)butyryloxy] 8 (3- methyl 2 octy1)2-(2 propynyl)-l,2,3,4-tetrahydro- SH- l benzopyrano 3,4-d] pyridine hydrochloride 0.8 g. (2.0 mmole) of 5,5-dimethyl-10-hydroxy-8-(3- methyl 2 octyl)-2-(2-propynyl)-1,2,3,4-tetrahydro-5H- [11benzopyrano[3,4-d1pyridine, 0.39 g. (2.0 mmoles) of 'y-diethylaminobutyric acid hydrochloride (F. F. Blicke, W. B. Wright and M. F. Zienty, J. Am. Chem. Soc. 63, 2488 (1941) and 0.45 g. (2.2 mmoles) of dicyclohexylcarbodiimide (Aldrich) were combined with 45 ml. of methylene chloride and stirred at room temperature overnight. The by-product of dicyclohexylurea was separated by filtration and the methylene chloride was removed using a rotary evaporator. The residue was dissolved in a mixture of methylene chloride/cyclohexane and filtered to remove any insoluble material. The solvents were evaponated and the residue dried in vacuo to give 0.8 g. (70%) of the product as a yellow powder. The desired product showed an R, of 0.4 on TLC in 10% methanol/chloroform. The IR and NMR spectra are consistent with the proposed structure.

Analysis: C34H53N203ClH20. Theory: H: 9.37; N=4.74. Found: C=69.86; H=9.53; N=4.99.

EXAMPLE 2 5,5 dimethyl-10-[4-(dimethylamino)butyryloxy1-8-(3- methyl-Z-octyl) 2 (2-propynyl)-1,2,3,4-tetrahydro-5H- [l]benzopyrano[3,4-d]pyridine is prepared according to the method of Example I by reacting equimolar quantities of 5,5 dimethyl-lO-hydroxy-S-(3-methyl-2-octyD-2- (2 propynyl)-l,2,3,4-tetrahydro 5H [l]benzopyrano- [3,4-d] pyridine with 'y-dimethylaminobutyric acid and dicyclohexylcarbodiimide.

EXAMPLE 3 10-[3-(dibutylamino)propionyloxy] 5,5 dimethyl-8- (3-methyl-2-octyl) 2 (2-propynyl)1,2,3,4-tetrahydro- 5H-[1]benzopyrano{3,4-d1pyridine hydrobromide is prepared according to the method of Example 1 by reacting equimolar quantities of 5,5-dimethyl 10 hydroxy-8-(3- methyl Z-octyD-Z-(Z-propynyD-l,2,3,4-tetrahydro-5I-I-[11 benzopyrano[3,4 d]pyridine with [3 dibutylaminopropionic acid hydrobromide and dicyclohexylcarbodiimide.

4 EXAMPLE 4 5,5 dimethyl-IO-(dipropylaminoacetyloxy)-8-n-pentyl- 2-(2-propynyl) l,2,3,4 tetrahydro-SH-[IJbenzopyrano- [3,4-d1pyridine tartrate is prepared according to the method of Example 1 by reacting equimolar quantities of 5,5-dimethyl 10 hydroxy-S-n-pentyl-Z-(Z-propynyl)- 1,2,3,4-tetrahydro 5H [1]benzopyrano[3,4-d]pyridine, dipropylaminoacetic acid tartrate and dicyclohexylcarbodiimide.

EXAMPLE 5 5,5-dimethyl l0 [S-(dipentylamino)valeryloxy]-8-(2- nonyl)-2-(2 propynyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-d]pyridine hydrochloride is prepared according to the method of Example 1 from equimolar amounts of 5,5 dimethyl-l0-hydroxy-8-(2-nonyl)-2-(2-propynyl)- l,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-d]pyridine, 6- dipentylaminovaleric acid hydrochloride and dicyclohexylcarbodiimide.

EXAMPLE 6 10-[4 (dihexylamino)butyryloxy] 2 (2-propynyl) 5,5,8-trimethyl 1,2,3,4 tetrahydro-5H-[llbenzopyrano- [3,4-d1pyridine is prepared according to the method of Example 1 from equimolar quantities of IO-hydroxy-Z- (2-propynyl)-5,5,8-trimethyl 1,2,3,4 tetrahydro-SH-[l] benzopyrano[3,4-d]pyridine, 'y-dihexylaminobutyric acid and dicyclohexylcarbodiimide.

EXAMPLE 7 2 benzyl-IO-[5-(diisopropyl)valeryloxy]-5,5-dimethyl- 8-(2 hexadecyl)-l,2,3,4-tetrahydro-5H-[ l]benzopyrano- [3,4-d1pyridine is prepared according to the method of Example 1 from equimolar amounts of 2benzyl-5,5-dimethyl-8-(2-hexadecyl)-l0-hydroxy 1,2,3,4 tetrahydro- 5H-[1]benzopyrano[3,4 d]pyridine 6-diisopropylaminovaleric acid and dicyclohexylcarbodiimide.

EXAMPLE 8 By reacting 2-benzyl-S,5-dimethyl l0 hydroxy-8-( 1- pentyl)-1,Z,3,4-tetrahydro 5H [1]benzopyrano[3,4-d] pyridine with equimolar amounts of ,B-diisobutylaminopropionic acid hydrochloride and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 2-benzyl-l0-[3-(dissobutylamino)propionyloxyJ- 5,5-dimethyl-8-(1 pentyl)-1,2,3,4-tetrahydro-5H-{1]benzopyrano[3,4-d] pyridine hydrochloride.

EXAMPLE 9 By reacting 2-cyc1obutylmethyl 5,5 dimethyl-8-(2-eicosyl)-10-hydroxy 1,2,3,4 tetrahydro-5H-[l1benzopyrano[3,4-d]pyridine with equimolar amounts of -diethylaminobutyric acid hydrobromide and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 2 cyclobutylmethyl-IO-[4-(diethylarnino)butyryloxy]-8-(2-eicosyl)-l,2,3,4-tetnahydro 5H [l]benzopyrano[3,4-d]pyridine hydrobromide.

EXAMPLE 10 By reaction 5,5-dimethyl-10-hydroxy-2-phenethyl-8-(2- tetradecyl)-l,2,3,4-tetrahydro-5H-[1]benzopyrano [3,4- d]pyridine with equimolar amounts of 'y-diethylaminobutyric acid hydrochloride and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 10-[4-(diethylamino)-butyryloxy]-5,5 dimethyl-Z-phenethyl-8-(2-tetradecyl) l,2,3,4 tetrahydro-SH-[Hbenzopyrano-[3,4-d]pyridine hydrochloride.

EXAMPLE 11 By reacting 2-allyl-5,5-diethyl-10-hydroxy-8-(Ii-methyl- 2-octyl)-l,2,3,4 tetrahydro 5H[1]benzopyrano-[3,4-d] pyridine with equimolar amounts of -diethylamino butyric acid acetate and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 2-a11yl-5,5-diethyl- 10 [4 (diethylamino)butyryloxy]- 1,2,3,4-tetrahydro 5H [l]benzopyrano[3,4-d]pyridine acetate.

EXAMPLE 12 By reacting 2-acety1-8-(3-cyclopropyl-2-propy1)-5,5-dimethyl--hydroxy-1,2,3,4 tetrahydro 5H [1]benzopyrano[3,4-d]pyridine with equimolar amounts of dipropylaminobutyric acid and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 2-acetyl-8-(3-cyclopropyl-2-propyl)-5,5 dimethyl-10-[4- (dipropylamino)butyryloxy] 1,2,3,4 -tetrahydro-5H-[1] benzopyrano [3,4-d] pyridine.

EXAMPLE 13 By reacting 8 cyclohexylethyl-Z-cyclopropylcarbonyl- 5,5-dimethyl-10-hydroxy 1,2,3,4 tetrahydro 5H-[11- benzopyrano[3,4d]pyridine with equimolar amounts of 'y dimethylaminobutyric acid hydrochloride and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 8cyclohexylethyl-2-cyclopropylcarbonyl-5,5-dimethyl 10-[4 (dimethylamino)butyryloxy]- 1,2,3,4-tetrahydro-5H- l 1 benzopyrano[3,4-d] pyridine hydrochloride.

EXAMPLE 14 By reacting 2-[l-(cis-3 chloro 2 propenyl]-5,5-dimethyl-10-hydroxy-8-(3-methyl-2-octyl) 1,2,3,4 tetrahydro-SH-[1]benzopyrano[3,4-d]pyridine with -diethylaminobutyric acid oleate and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 2-[1-(cis-3-chloro-2-propenyl)] 10 [4-(diethylamino) butyryloxy]-5,5-dimethyl-8-(3-methyl 2 octyl)-l,2,3,4- tetrahydro-5H-[ 1 benzopyrano [3,4-d] pyridine oleate.

EXAMPLE 15 By reacting 5,5-dimethyl-8-(2 heptyl)-10-hydroxy-2- [2-(4-methylphenethyl)] 1,2,3,4 tetrahydro 5H-[l]- benzopyrano[3,4-d]pyridine with equimolar amounts of fl-diethylaminopropionic acid hydrochloride and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 10-[3-(diethylamino)propionyloxy]- 5,5-dimethyl-8-(2-heptyl) 2 [2-(4-methylphenethyl)]- 1,2,3,4-tetrahydro 5H [1]benzopyrano[3,4-d]pyridine hydrochloride.

EXAMPLE 16 By reacting 5,5-dimethyl-10-hydroxy 2 (3-methyl-2- octyl)-1,2,3,4-tetrahydro 5H [1]benzopyrano[3,4-d]- pyridine with equimolar amounts of 'y diethylaminobutyric acid tosylate and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 10-[4-(diethylamino)-butyryloxy]-5,5-dimethyl 2 (3- methyl 2 butenyl) 8 (3 methyl 2 octyl)-l,2,3,4- tetrahydro-SH- 1 benzopyrano[ 3,4-d] pyridine tosylate.

EXAMPLE 17 By reacting 5,5-dimethyl-10-hydroxy 8 (3-methyl-2- octyl)-2-{'4[1-(3-sulfamylphenyl) 1 butenyl] }-1,2,3,4- tetrahydro-5H-[1]benzopyrano[3,4-d]pyridine with equimolar amounts of fl-diisopropylaminopropionic acid and dicyclohexylcarbodiimide, in accordance with the method of Example 1, there is obtained 5,5-dimethyl-10-[3-(diisopropylamino)propionyloxy] 2 {4 [1 (3 sulfamylphenyl)-l-butenyl]} 1,2,3,4 tetrahydro-5H-[1]benzopyrano [3 ,4-d pyridine.

EXAMPLE 18 By reacting 5,5 dimethyl 10 hydroxy 8 (3- methyl 2 octyl) 2 {3-(4-acetylaminophenyl)-1- butenyl]} 1,2,3,4 tetrahydro 5H [1]benzopyrano- [3,4-d]pyridine with equimolar amounts of 'y diethylaminobutyric acid hydrochloride and dicyclohexylcorbodiimide according to the method of Example 1 there is obtained 10 [4 (diethylamino)butyryloxy] 5-5 dimethyl-8-(3-methyl-2-octyl)-2-{3 [1 (4 acetylaminophenyl) 1 butenyl]} 1,2,3,4 tetrahydro 5H-[1]- pyridine hydrochloride.

EXAMPLE 19 EXAMPLE 20 By reacting 8 cyclopropyl 5,5 dimethyl 10 hydroxy 2 propionyl 1,2,3,4 tetrahydro-SH-[lJbenzopyrano[3,4-d]pyridine with equimolar amounts of 'y-diethylaminobutyric acid citrate and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 8 cyclopropyl 10 [4 (diethylamino)- butyryloxy] 5,5 dimethyl 2 propionyl 1,2,3,4- tetrahydro 5H [1]benzopyrano[3,4-d] pyridine citrate.

EXAMPLE 21 By reacting 2 cinnamyl 8 cyclopropylmethyl-5,5- dimethyl 10 hydroxy 1,2,3,4 tetrahydro 5H [1]- benzopyrano[3,4-d]pyridine with equimolar amounts of 'y diethylaminobutyric acid succinate and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 2 cinnamyl 8 cyclopropylmethyl- 10 [4 (diethylamino)butyryloxy] 5,5 dimethyl- 1,2,3 ,4 tetrahydro 5H [1]benzopyrano[3,4-d]pyridine succlnate.

EXAMPLE 22 By reacting 5,5 dimethyl 10 hydroxy 2 [2 (4- methylmercaptophenethyl)] 8 (3 methyl 2 octyl)- 1,2,3,4 tetrahydro-5H [l]benzopyrano-[3,4-d]pyridine with 'y diethylaminobutyric acid lactate and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 10 [4 (diethylamino)butyryloxy]- 5,5-dimethyl 8 (3 methyl 2 octyl)-2-[2-(4-methylmercaptophenethyl)] 1,2,3,4 tetrahydro 5H [1]- benzopyrano [3,4-d] pyridine lactate.

EXAMPLE 23 By reacting 5,5-dimethyl-lO-hydroxy-S-(3-methyl-2- octyl) 2 [4 (4-nitrophenylbutyl)]-1,2,3,4-tetrahydro- 5H [1]benzopyrano[3,4 d]pyridine with equimolar amounts of 'y-diethylaminobutyric acid hydrochloride and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 10-[4-(diethylamino)butyryloxy]-5,5-dimethyl 8 (3 methyl-2-octyl)-2-[4-(4-nitrophenylbutyl] 1,2,3,4 tetrahydro 5H [1]benzopyrano [3,4 d]pyridine hydrochloride.

EXAMPLE 24 By reacting 5,5-di-(l-hexyl)-10-hydroxy-8-rnethyl-2- [3-(1 propynyl)] 1,2,3,4 tetrahydro 5H [1]benzopyrano[3,4-d]pyridine with equimolar amounts of 'y-di ethylaminobutyric acid hydrochloride and dicyclohexylcarbodiimide, according to the method of Example 1, there is obtained 10-[4-(diethylamino)butyryloxy]-5,5-di- (l-hexyl) 8 methyl 2 [3-(1-propynyl)]-1,2,3,4-tetrahydr0-5H-[ 1]benzopyrano [3,4-d] pyridine hydrochloride.

The present invention includes within its scope pharmaceutical compositions comprising, as an active ingredient, at least one of the compounds of this invention in association with a pharmaceutical carrier or diluent. The compounds of this invention exhibit both oral and parenteral activity and can be formulated in dosage forms for oral, parenteral, or rectal administration.

Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound is admixed with at least one inert diluent such as sucrose, lactose or starch. Such dosage forms can also comprise, as is normal practice, additional substances other than inert diluents, e.g., lubricating agents such as magnesium stearate. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.

Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs containing inert diluents commonly used in the art, such as water. Besides inert diluents, such compositions can also include adjuvants, such as wetting agents, emulsifying and suspending agents and sweetening, flavoring and perfuming agents.

Preparations according to this invention for parenteral administration include sterile aqueous or nonaqueous solutions, suspensions, or emulsions. Examples of nonaqueous solvents or vehicles are propylene glycol, polyethylene glycol, vegetable oils, such as olive oil, and injectable organic esters such as ethyl oleate. Such dosage forms may also contain adiuvants such as preserving, wetting, emulsifying and dispersing agents. They may be sterilized by, for example, filtration through a bacteriaretaining filter, by incorporating sterilizing agents into the compositions, by irradiating the compositions, or by heating the compositions. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately before use.

Compositions for rectal administration are suppositories which may contain in addition to the active substance,

excipients such as cocoa butter or a suppository wax.

The dosage of active ingredient in the compositions of this invention may be varied; however, it is necessary that the amount of the active ingredient shall be such that a suitable dosage form is obtained. The selected dosage depends upon the desired therapeutic effect, on the route of administration and on the duration of the treatment. Generally, oral dosage levels of between 0.5 and 250 ing/kg. of body Weight daily are administered to patients suffering from depression. Preferred dosages are oral dosages of from to 25 mg./kg.

The following example further illustrates the pharmaceutical compositions which are a feature of this invention:

EXAMPLE 25 Tablets weighing 500 mg. and having the following compositions are prepared by standard tableting procedures:

Ingredient:

5,5 dimethyl 10 [4 (diethylamino) butyryloxy]- 8 (3 methyl 2 octyl)-2-(2-propynyl)-1,2,3,4- tetrahydro 5H [l]benzopyrano[3,4 d] pyridine 8 We claim: 1. A compound of the formula obwnnm .l O. R, 0/

7 0 g (CH2) nN\ 4 Kai Ra R, 0/

wherein R is loweralkynyl; R is loweralkyl; R is C -C alkyl or cycloalkylloweralkyl; n is an integer from 1 to 6; R is hydrogen or loweralkyl; or a pharamceutically acceptable acid addition salt thereof.

4. A compound in accordance with claim 3 wherein R is propynyl.

5. A compound in accordance with claim 4: 5,5-dimethyl 10 [4-(diethylarnino)butyryloxy]-8-(3-methyl- 2-octyl) 2 (2- propynyl) l,2,3,4- tetrahydro-SH-[l] benzopyrano[3,4-d]pyridine or a pharmaceutically acceptable acid solution salt thereof.

6. A compound in accordance with claim 5: 5,5-dimethyl 10 [4-(diethylamino)butyryloxy] -8-(3-methyl- 2-octy1) 2 (2- propynyl) 1,2,3,4- tetrahydro-SH-[l] benzopyrano[3,4-d]pyridine hydrochloride.

References Cited UNITED STATES PATENTS 3,429,889 2/1969 Shulgin 260295 T ALAN L. ROTMAN, Primary Examiner US. Cl. X.R.

260-240 D, 240 I, 240 TC; 424266 Patent No.

Inventor(s) Dated January 22, 1974 Harry George Pars and Raj Kumar Razdan It is certified that error appears in the above-identified patent .and that said Letters Patent are hereby corrected as shown below:

Column 2,

line

line

line

line

line

Column 5,

line

line

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Column 6,

.Column 8,

line

line 1,-

"pyropylene" should be propylene "dimide" should be diimide after "pyridine" a comma should be inserted;

"dissobutylamino" should be diisobutylamino 1 "reaction" should be reacting after "3-methyl2" insert butenyl)8-(3methyl2 change "dicyclohexylcorbo" to dicyclohexylcarbo after "5H[l]" insert benzopyrano [3,4-d]

change{"pharamceutically" to pharmaceutically Signed and sealed this 25th day of June 197M.-

(SEAL) Attest:

EDWARD M.FLETCHER,JR. Attesting Officer C. MARSHALL DANN Commissioner of Patents 

